1. Field of the Invention
Membrane-coated sustained-release tablets, such membrane-coated tablets having a water-soluble pore-creating substance distributed in the membrane coating.
2. Prior Art
The prior art is replete with innumerable sustained-release pharmaceutical compositions, including membrane-coated sustained-release tablets, which have had greater or lesser degrees of success and which accomplish the desired result, namely, the attainment of a substantially constant and sustained dissolution rate during a major portion of their dissolution time when exposed to gastro-intestinal fluids, to a greater or lesser extent. Some of the prior-art membrane-coated sustained-release tablets comprised a water-soluble pore-creating substance in the membrane coating for the creation of pores therein to assist with the entering of gastrointestinal fluids into the membrane for dissolution of the tablet therewithin and subsequent emission of the dissolved tablet, including the drug or medicament therein, in solution form into the system. Representative of prior art attempts to provide a superior membrane-coating and membrane-coated sustained-release pharmaceutical tablet include Hotko, et al. U.S. Pat. No. 3,325,365, issued June 13, 1967, covering an enteric tablet having compressed onto the core a solid granulate composition comprising the physiological active material and the enteric coating. Mention may also be made of Groppenbacher, et al., U.S. Pat. Nos. 4,060,598 and 3,935,326, Polli, et al., 3,538,214 of Merck issued Nov. 3, 1979, as well as Daum, et al., U.S. Pat. No. 3,420,931, and British Pat. No. 1,186,990 of Ercopharm A/S. These patents in general approach the problem of membrane-coated sustained-release compositions, including tablets, from the standpoint of employing a pore-creating substance in one way or another, employing different types of insoluble polymers as the membrane-coating, varying the number of coats, varying the pore-creating substance, et cetera ad infinitum, but with less than satisfactory results. This is evidenced by the constantly increasing efforts to modify the approach and the technology for purposes of improving the result, but almost always with a concomitant increase in complexity of the product, the technique, and of course with increased cost. Accordingly, there exists a clear and ever-increasing demand for a simple but still highly effective and superior sustained-release tablet which will exhibit a substantially constant dissolution rate over an extended period of time and during a major portion of its dissolution time when exposed to gastrointestinal fluids of the subject to whom or to which administered, and the fulfillment of this demand is one of the objects of the present invention, as will become more fully apparent hereinafter. This object of the invention is accomplished by the provision of the novel membrane-coated sustained-release tablets of the present invention and the method of producing the same and is possible due to the discovery of unique and valuable characteristics of a particular terpolymer which is used as the water-insoluble and gastrointestinal fluid-insoluble membrane coating for the sustained-release tablets of the invention and which, together with the pore-creating substance randomly distributed therethrough, imparts highly desirable and superior characteristics of dissolution rate and, accordingly, also blood levels, to the particular membrane-coated sustained-release pharmaceutical tablets of the present invention.
A further disadvantage of the membranes or coatings of the prior art has been their inadequate adhesion characteristics with respect to tablets having both high and low energy surfaces, and this shortcoming is likewise overcome by provision of the method and product of the invention, according to which the membrane coating adheres tenaciously to both high and low energy tablet surfaces.
The employment of the terpolymers of the present invention as the membrane-coating for sustained-release tablets, and the extremely valuable characteristics thereof when combined with the water-soluble pore-creating substance, have not previously been suggested in the prior art, nor has it been suggested that the excellent adhesion, dissolution rates, and blood levels could be attainable with any membrane-coated sustained-release tablet wherein such terpolymers are employed as the water-insoluble and gastrointestinal fluid-insoluble membrane coating. This is although the terpolymers of the present invention are known materials from U.S. Pat. Nos. 3,595,939, 3,444,122, and 2,852,499, Federal Republic of Germany Pat. No. 1 087 353 of Aug. 18, 1960, British Patent Specification No. 862 978 published Mar. 15, 1961, and British Patent Specification No. 883 070 published Nov. 22, 1961, or from one of the following Chemical Abstracts references: CA 71, 103242a, CA 71, 14276x (1969), and CA 83, 180527x (1975).